Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, United States; Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, United States; Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, United States
School of Biosciences, University of Sheffield, Sheffield, United Kingdom; Bateson Centre, University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, University of Sheffield, Sheffield, United Kingdom
The tuberal hypothalamus controls life-supporting homeostatic processes, but despite its fundamental role, the cells and signalling pathways that specify this unique region of the central nervous system in embryogenesis are poorly characterised. Here, we combine experimental and bioinformatic approaches in the embryonic chick to show that the tuberal hypothalamus is progressively generated from hypothalamic floor plate-like cells. Fate-mapping studies show that a stream of tuberal progenitors develops in the anterior-ventral neural tube as a wave of neuroepithelial-derived BMP signalling sweeps from anterior to posterior through the hypothalamic floor plate. As later-specified posterior tuberal progenitors are generated, early specified anterior tuberal progenitors become progressively more distant from these BMP signals and differentiate into tuberal neurogenic cells. Gain- and loss-of-function experiments in vivo and ex vivo show that BMP signalling initiates tuberal progenitor specification, but must be eliminated for these to progress to anterior neurogenic progenitors. scRNA-Seq profiling shows that tuberal progenitors that are specified after the major period of anterior tuberal specification begin to upregulate genes that characterise radial glial cells. This study provides an integrated account of the development of the tuberal hypothalamus.
